The facile synthesis of 1,2,3-trisubstituted pyrroles from the reaction of
chlorocarbenes with 1-azabuta-1,3-dienes
Yuri N. Romashin,a Michael T. H. Liu*a and Roland Bonneaub
a Department of Chemistry, University of Prince Edward Island, P.E.I.,Canada C1A 4P3. E-mail: liu@upei.ca
b LPCM, Laboratoire de Chimie Physique A, Universite´ de Bordeaux 1, 33405 Talence Cedex, France
Received (in Corvallis, OR, USA) 4th December 1998, Accepted 4th January 1999
Table 1 Isolated yields for 1,2,3-trisubstituted pyrroles 6
1,2,3-Trisubstituted pyrroles have been synthesized in good
yield from the reaction of chlorocarbenes with 1-azabuta-
1,3-dienes.
Yield (%)
Product 6
Ar
R1
R2
Mp/°C
hn
Heat
Carbenes and metal carbenoids are useful intermediates in the
synthesis of nitrogen-containing heterocyclic compounds of
biological importance. Most of the work has been devoted to the
reactions of carbenes and metal carbenoids with azomethines
that result in aziridines, pyrrolidines, oxazolidines and b-
lactams.1,2 The literature has only two examples where pyrroles
appeared as the end product.3,4 Introducing dimethyl acet-
ylenedicarboxylate to a reaction mixture of N-benzylideneani-
line and dichlorocarbene, generated by alkaline hydrolysis of
CHCl3, results in the formation of a pyrrole derivative in low
yield.3 Thermolysis of chromium carbene complexes with
1-azabuta-1,3-dienes leads to the formation of 1,2,3-trisub-
stituted pyrroles in good yield.4 However, no pyrroles could be
detected in the reaction of dichlorocarbene with 1-azabuta-
1,3-dienes, where dichloroaziridines were isolated in high
yield.3,5 Pyrroles represent an important major class of
heterocycles. Their prominence encourages the continuing
evolution of new synthetic methods.6 Our experiments pro-
duced a facile one-step synthesis of 1,2,3-trisubstituted pyrroles
based on the reaction of arylchlorocarbenes with a variety of
1-azabuta-1,3-dienes under photolytic or thermal conditions.
We propose that the reaction of singlet carbene such as
arylchlorocarbene with 1-azabuta-1,3-dienes goes through an
azomethine ylide3 4 via a reaction between the vacant 2p-orbital
of the carbene and the nitrogen non-bonding electron pair
(Scheme 1). The formed ylide then undergoes intramolecular
ring-closure to form a dihydropyrrole 5, followed by HCl
elimination to produce pyrroles.
a
b
c
d
e
f
Ph
Me
Me
Me
Bn
Bn
Bn
Bn
Ph
Ph
Ph
Ph
Ph
Ph
Me
96–96.5
95–96
50
51
48
40
55
50
30
54
65
52
50
58
56
40
p-MeC6H4
p-ClC6H4
Ph
p-MeC6H4
p-ClC6H4
p-MeC6H4
112–113
116–117a
132–133
147–148
viscous oil
g
a Only the mp for 6d has been reported: lit., 117–118 °C (ref. 6).
1-azabuta-1,3-dienes 3 (R1 = Me, Bn; R2 = Me, Ph) from
cinnamaldehyde or crotonaldehyde and methyl or benzyl
amines. We purified them by distillation under reduced
pressure. The chlorocarbenes 2 react rapidly with 1-azabuta-
1,3-dienes 3 to presumably yield dihydropyrroles 5. In all cases,
the elimination of HCl from 5 to give pyrroles 6 is instantaneous
since no trace of 5 could be found. Yields and melting points of
pyrroles 6 are presented in Table 1 and their spectral data8
compare well with those previously reported for 6a,d.2,6,9 The
yields of pyrroles 6 obtained from photolysis (30–55%) and
thermolysis (40–65%) are comparable.†
Photolyses were carried out by irradiation (350 nm) of
solutions of the chlorodiazirines 1 (1 mmol) and 1-azabuta-
1,3-dienes 3 (2.5 mmol) in hexane (50 ml) at 25 °C for 24 h. For
the thermolysis reactions solutions of chlorodiazirines 1 (1
mmol) and the 1-azabuta-1,3-dienes 3 (2.5 mmol) were refluxed
in absolute benzene (10 ml) for 3 h. After workup, the pyrroles
6 were purified by column chromatography on silica gel with
hexane–Et2O (10:1) as eluent, followed by crystallization from
PriOH–hexane (1:3).
The arylchlorocarbenes 2 were generated from arylchloro-
diazirines 17 by photolysis or thermolysis. We prepared the
M. T. H. Liu wishes to thank the NSERC of Canada for
generous financial support.
:
R1
Ar
R2
N
+
R1
Cl
C
N
Ar
Cl
N
N
–
Ar
Cl
hν or heat
3
C
C:
–N2
Notes and references
† All compounds reported herein gave satisfactory microanalysis data.
1
2
R2
4
1 A. Padwa and M. D. Weingarten, Chem. Rev., 1996, 96, 223; A. Padwa
and S. F. Hornbruckle, Chem. Rev., 1991, 91, 263; A. F. Khlebnikov and
R. R. Kostikov, Russ. Chem. Bull., 1993, 42, 653; M. P. Doyle and D. C.
Forbes, Chem. Rev., 1998, 98, 911; L. S. Hegedus, J. Montgomery, Y.
Narukawa and D. S. Snustad, J. Am. Chem. Soc., 1991, 113, 5784.
2 E. Vedejs and J. W. Grissom, J. Am. Chem. Soc., 1988, 110, 3238.
3 R. R. Kostikov, A. F. Khlebnikov and V. Y. Bespalov, J. Phys. Org.
Chem., 1993, 6, 83.
R2
Ar
R1
Cl
N
Ar
–HCl
N
R2
R1
5
6
a Ar = Ph, R1 = Me, R2 = Ph
4 T. N. Danks and D. Velo-Rego, Tetrahedron Lett., 1994, 35, 9443.
5 R. R. Kostikov, A. F. Khlebnikov and K. A. Ogloblin, Zh. Org. Khim.,
1977, 13, 1857.
6 B. M. Trost and E. Keinan, J. Org. Chem., 1980, 45, 2741.
7 W. H. Graham, J. Am. Chem. Soc., 1965, 87, 4396.
8 Selected data for 6a: dH(60 MHz, CDCl3) 3.53 (3H, s), 6.46 (1H, d, J 3),
6.76 (1H, d, J 3), 7.1–7.5 (10H, m). For 6b: dH (60 MHz, CDCl3) 2.33
(3H, s), 3.47 (3H, s), 6.38 (1H, d, J 3), 6.72 (1H, d, J 3), 7.1–7.4 (9H, m).
For 6c: dH(60 MHz, CDCl3) 3.48 (3H, s), 6.43 (1H, d, J 3), 6.76 (1H, d,
b Ar = p-MeC6H4, R1 = Me, R2 = Ph
c Ar = p-ClC6H4, R1 = Me, R2 = Ph
d Ar = Ph, R1 = Bn, R2 = Ph
e Ar = p-MeC6H4, R1 = Bn, R2 = Ph
f
Ar = p-ClC6H4, R1 = Bn, R2 = Ph
g Ar = p-MeC6H4, R1 = Bn, R2 = Me
Scheme 1
Chem. Commun., 1999, 447–448
447
Romashin, Yuri N.
